The objective of this proposal is to determine the role of costimulatory signals (CD28/B7, CD40L/CD40) in the pathogenesis of allergic airway inflammation and hyperresponsiveness (AHR). We have found that inhibition of T cell activation with CTLA4-Ig (a fusion protein which blocks costimulation) prevents the induction of allergic AHR in a murine model. Our hypothesis is that costimulatory signals are critical in the development of allergen induced AHR. We will dissect the mechanisms by which costimulatory molecules regulate allergen induced AHR using transgenic knock-out mice, fusion proteins and monoclonal antibodies. As appropriate, we will compare our findings from the model of allergen induced pulmonary inflammation to a model of contact hypersensitivity (CHS). Thus, paradigms learned from these models with interruption of costimulation may be applicable to other T cell mediated diseases, including other skin diseases.